These studies are designed to determine the ability of various substances to induce HbF synthesis in experimental animals and humans. Because of its safety and demonstrated activity, we have initiated an expanded phase I-II study of hydroxyurea. The purpose of this study is to further define the frequency and magnitude of the response of individual patients and to identify significant toxicity. During the past several years various hematopoietic growth factors have been molecularly cloned and large quantities of purified, biologically active material are available for clinical testing. Those growth factors with demonstrated activity on erythroid precursors, such as erythropoietin, IL3 and GM-CSF, have the potential for stimulating HbF synthesis. Our studies in Rhesus monkeys have shown that erythropoietin increases HbF production modestly when administered alone, but may be augmented by a preceeding course of hydroxyurea, IL3 or GM-CSF.